Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Differential translation efficiency of orthologous genes is involved in phenotypic divergence of yeast species

A Corrigendum to this article was published on 01 May 2007

This article has been updated


A major challenge in comparative genomics is to understand how phenotypic differences between species are encoded in their genomes. Phenotypic divergence may result from differential transcription of orthologous genes, yet less is known about the involvement of differential translation regulation in species phenotypic divergence. In order to assess translation effects on divergence, we analyzed 2,800 orthologous genes in nine yeast genomes. For each gene in each species, we predicted translation efficiency, using a measure of the adaptation of its codons to the organism's tRNA pool. Mining this data set, we found hundreds of genes and gene modules with correlated patterns of translational efficiency across the species. One signal encompassed entire modules that are either needed for oxidative respiration or fermentation and are efficiently translated in aerobic or anaerobic species, respectively. In addition, the efficiency of translation of the mRNA splicing machinery strongly correlates with the number of introns in the various genomes. Altogether, we found extensive selection on synonymous codon usage that modulates translation according to gene function and organism phenotype. We conclude that, like factors such as transcription regulation, translation efficiency affects and is affected by the process of species divergence.

NOTE: In the original version of this paper, subpanels 2c and d were switched, resulting in incorrect information in the legend. Figure 2c shows genes of the tricarboxylic acid (TCA) cycle, while Figure 2d shows glycolysis genes. The error has been corrected in the HTML and PDF versions of the article.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Comparison of the tRNA gene repertoires of S. cerevisiae and Y. lipolytica.
Figure 2: The translation efficiency profiles of mitochondrial and cytosolic ribosomal proteins, glycolysis and the tricarboxylic acid cycle show coherent patterns.
Figure 3: Scheme for testing for a species effect on translation efficiency for a group of genes.
Figure 4: The translation efficiency profiles of genes related to mRNA splicing correlate with the number of introns in the genomes of species.

Similar content being viewed by others

Change history

  • 28 March 2007

    NOTE: In the original version of this paper, subpanels 2c and d were switched, resulting in incorrect information in the legend. Figure 2c shows genes of the tricarboxylic acid (TCA) cycle, while Figure 2d shows glycolysis genes. The error has been corrected in the HTML and PDF versions of the article.


  1. Wolfe, K.H. Comparative genomics and genome evolution in yeasts. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361, 403–412 (2006).

    Article  CAS  Google Scholar 

  2. Gompel, N., Prud'homme, B., Wittkopp, P.J., Kassner, V.A. & Carroll, S.B. Chance caught on the wing: cis–regulatory evolution and the origin of pigment patterns in Drosophila. Nature 433, 481–487 (2005).

    Article  CAS  Google Scholar 

  3. Ihmels, J. et al. Rewiring of the yeast transcriptional network through the evolution of motif usage. Science 309, 938–940 (2005).

    Article  CAS  Google Scholar 

  4. Powers, D.A. & Schulte, P.M. Evolutionary adaptations of gene structure and expression in natural populations in relation to a changing environment: a multidisciplinary approach to address the million-year saga of a small fish. J. Exp. Zool. 282, 71–94 (1998).

    Article  CAS  Google Scholar 

  5. dos Reis, M., Savva, R. & Wernisch, L. Solving the riddle of codon usage preferences: a test for translational selection. Nucleic Acids Res. 32, 5036–5044 (2004).

    Article  CAS  Google Scholar 

  6. Sharp, P.M. & Li, W.H. The codon adaptation index–a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res. 15, 1281–1295 (1987).

    Article  CAS  Google Scholar 

  7. Percudani, R., Pavesi, A. & Ottonello, S. Transfer RNA gene redundancy and translational selection in Saccharomyces cerevisiae. J. Mol. Biol. 268, 322–330 (1997).

    Article  CAS  Google Scholar 

  8. Lowe, T.M. & Eddy, S.R. tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res. 25, 955–964 (1997).

    Article  CAS  Google Scholar 

  9. Tanay, A., Regev, A. & Shamir, R. Conservation and evolvability in regulatory networks: the evolution of ribosomal regulation in yeast. Proc. Natl. Acad. Sci. USA 102, 7203–7208 (2005).

    Article  CAS  Google Scholar 

  10. Ghaemmaghami, S. et al. Global analysis of protein expression in yeast. Nature 425, 737–741 (2003).

    Article  CAS  Google Scholar 

  11. Fraser, H.B., Hirsh, A.E., Wall, D.P. & Eisen, M.B. Coevolution of gene expression among interacting proteins. Proc. Natl. Acad. Sci. USA 101, 9033–9038 (2004).

    Article  CAS  Google Scholar 

  12. Lithwick, G. & Margalit, H. Relative predicted protein levels of functionally associated proteins are conserved across organisms. Nucleic Acids Res. 33, 1051–1057 (2005).

    Article  CAS  Google Scholar 

  13. Rice, J. Mathematical Statistics and Data Analysis (Wadsworth Publishing Company, Belmont, Calfiornia, 1995).

    Google Scholar 

  14. Harris, M.A. et al. The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 32, D258–D261 (2004).

    Article  CAS  Google Scholar 

  15. Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate – a practical and powerful approach to multiple testing. J. R. S. Soc. Ser. B. Methodol. 57, 289–300 (1995).

    Google Scholar 

  16. Nantel, A. The long hard road to a completed Candida albicans genome. Fungal Genet. Biol. 43, 311–315 (2006).

    Article  CAS  Google Scholar 

  17. Barth, G. & Gaillardin, C. Physiology and genetics of the dimorphic fungus Yarrowia lipolytica. FEMS Microbiol Rev 19, 219–237 (1997).

    Article  CAS  Google Scholar 

  18. Braun, B.R. et al. A human-curated annotation of the Candida albicans genome. PLoS Genet 1, 36–57 (2005).

    Article  CAS  Google Scholar 

  19. Kellis, M., Birren, B.W. & Lander, E.S. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. Nature 428, 617–624 (2004).

    Article  CAS  Google Scholar 

  20. Berbee, M. & Taylor, J. Systematics and evolution. in The Mycota, Vol. VIIB (eds. McLaughlin, D., McLaughlin, E. & Lemke, P.) 229–245 (Springer, Berlin, 2001).

    Google Scholar 

  21. Arnaud, M.B. et al. Sequence resources at the Candida Genome Database. Nucleic Acids Res. 35, D452–D456 (2007).

    Article  CAS  Google Scholar 

  22. Issel-Tarver, L. et al. Saccharomyces Genome Database. Methods Enzymol 350, 329–346 (2002).

  23. Galagan, J.E. et al. Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. fumigatus and A. oryzae. Nature 438, 1105–1115 (2005).

    CAS  Google Scholar 

  24. Pruess, M., Kersey, P. & Apweiler, R. The Integr8 project–a resource for genomic and proteomic data. In Silico Biol. 5, 179–185 (2005).

    Article  CAS  Google Scholar 

  25. Kanz, C. et al. The EMBL Nucleotide Sequence Database. Nucleic Acids Res. 33, D29–D33 (2005).

    Article  CAS  Google Scholar 

  26. Segal, E. et al. A genomic code for nucleosome positioning. Nature 442, 772–778 (2006).

    Article  CAS  Google Scholar 

  27. Wright, F. The 'effective number of codons' used in a gene. Gene 87, 23–29 (1990).

    Article  CAS  Google Scholar 

  28. Alexeyenko, A., Tamas, I., Liu, G. & Sonnhammer, E.L. Automatic clustering of orthologs and inparalogs shared by multiple proteomes. Bioinformatics 22, e9–e15 (2006).

    Article  CAS  Google Scholar 

  29. Prillinger, H. et al. Phylogeny and systematics of the fungi with special reference to the Ascomycota and Basidiomycota. Chem. Immunol. 81, 207–295 (2002).

    Article  Google Scholar 

Download references


We thank the Pilpel laboratory for helpful discussions and E. Segal, A. Regev, I. Tirosh, Y. Gilad, N. Barkai, J. Moult and J.L. Sussman for discussions and critical reviews of the manuscript. Y.P. holds the Rothstein Career Development Chair in Genetic Diseases. We thank the Ben May Charitable Trust and EMBRACE, the European Union Network of Excellence in Bioinformatics for grant support.

Author information

Authors and Affiliations



Y.P. and O.M. conceived the study, and Y.P. supervised the study. O.M. and Y.P. designed the analyses, O.M. performed the analyses and O.M. and Y.P. wrote the paper.

Corresponding author

Correspondence to Yitzhak Pilpel.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

The relationship between translation efficiency (tAI) and protein levels. (PDF 224 kb)

Supplementary Fig. 2

Physically interacting proteins tend to have similar translation efficiencies across species. (PDF 90 kb)

Supplementary Fig. 3

Clustering of the multispecies translation efficiency profiles. (PDF 407 kb)

Supplementary Fig. 4

Comparison of the effective number of codons (Nc) and the tRNA adaptation index (tAI) for the coding sequences of ten ascomycotic yeast species. (PDF 223 kb)

Supplementary Fig. 5

Translation efficiency profiles of genes related to M-phase of the cell cycle. (PDF 92 kb)

Supplementary Table 1

The tRNA repertoires of the analyzed species. (PDF 76 kb)

Supplementary Table 2

Translation efficiency profiles of orthologous genes across species, their division into 40 clusters, and the functional enrichment within clusters. (PDF 562 kb)

Supplementary Methods (PDF 173 kb)

Supplementary Note (PDF 137 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Man, O., Pilpel, Y. Differential translation efficiency of orthologous genes is involved in phenotypic divergence of yeast species. Nat Genet 39, 415–421 (2007).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing